The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light.
We have identified a novel component of the circadian clock that regulates its sensitivity to light at the evening light to dark transition. USP2 (Ubiquitin Specific Protease 2), which de-ubiquitinylates and stabilizes target proteins, is rhythmically expressed in multiple tissues including the SCN. We have developed a knockout model of ... USP2 and found that exposure to low irradiance light at ZT12 increases phase delays of USP2(-/-) mice compared to wildtype. We additionally show that USP2b is in a complex with several clock components and regulates the stability and turnover of BMAL1, which in turn alters the expression of several CLOCK/BMAL1 controlled genes. Rhythmic expression of USP2 in the SCN and other tissues offers a new level of control of the clock machinery through de-ubiqutinylation and suggests a role for USP2 during circadian adaptation to environmental day length changes.
Mesh Terms:
ARNTL Transcription Factors, Animals, Blotting, Western, CLOCK Proteins, Cell Line, Circadian Rhythm, Endopeptidases, Female, Humans, Immunoprecipitation, Light, Liver, Male, Mice, Mice, Knockout, NIH 3T3 Cells, Period Circadian Proteins, Polymerase Chain Reaction, Retina, Suprachiasmatic Nucleus
ARNTL Transcription Factors, Animals, Blotting, Western, CLOCK Proteins, Cell Line, Circadian Rhythm, Endopeptidases, Female, Humans, Immunoprecipitation, Light, Liver, Male, Mice, Mice, Knockout, NIH 3T3 Cells, Period Circadian Proteins, Polymerase Chain Reaction, Retina, Suprachiasmatic Nucleus
PLoS ONE
Date: Oct. 04, 2011
PubMed ID: 21966515
View in: Pubmed Google Scholar
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